Several models of increased epidermal proliferation have associated abnormalities of differentiation: low calcium keratinocyte cultures, essential fatty acid deficiency and psoriasis. One possible common feature in these models is abnormal Arachidonic acid (AA) metabolism. Initial studies have revealed a fourth in vitro model where increased proliferation is associated with increased AA metabolism keratinocyte cultures which are non-confluent. On these non-confluent cultures, AA metabolism has been shown to modulate their rate of proliferation. This proposal is designed to specifically delineate the roles of the AA metabolic pathway in epidermal keratinocyte proliferation and differentiation in each of these models in vitro: non-confluence, low calcium, essential fatty acid deficiency and psoriasis. A better understanding of how AA metabolism modulates epidermal function may lead to improved therapy for diseases such as psoriasis. Through the execution of the studies described in the proposed project, Dr. Pentland will learn and refine skills in lipid chemistry, separational science, tissue culture, enzyme kinetics, immunoassay, and HPLC. This training will provide the necessary background for Dr. Pentland to become a competent and independent clinical investigator. In addition, the link between the Department of Pharmacology and Dermatology provided by the project outlined will enrich and diversify the research environment of both departments.